Cronbach Nicola, Méjécase Cécile, Moosajee Mariya
UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK.
Pharmaceuticals (Basel). 2025 Sep 9;18(9):1352. doi: 10.3390/ph18091352.
Twenty causative genes have been reported that cause non-syndromic childhood glaucoma associated with anterior segment dysgenesis. , and are the most well-known, but cases linked to , and have also been reported. As genetic testing becomes increasingly widespread and rates of molecular diagnosis rise, the extent of phenotypic overlap between the different genetic causes of non-syndromic glaucoma associated with anterior segment dysgenesis is becoming more evident. Taking aniridia as an example, whilst mutations remain the predominant cause, variants in , , and have also been reported in patients with childhood glaucoma and aniridia. Developments in molecular-based therapies for retinal and corneal disease are advancing rapidly, and pre-clinical studies of gene-based treatments for glaucoma and aniridia are showing promising results. Use of adeno-associated viral vectors for gene delivery is most common, with improvements in intraocular pressure and retinal ganglion cell survival in Tg- mouse models of glaucoma, and successful correction of a germline nonsense variant in mice using CRISPR-Cas9 gene editing. This review will explore the actions and interactions of the genetic causes of non-syndromic glaucoma associated with anterior segment dysgenesis and discuss the current developments in molecular therapies for these patients.
已经报道了20个导致与前段发育异常相关的非综合征性儿童青光眼的致病基因。 、 和 是最广为人知的，但与 、 和 相关的病例也有报道。随着基因检测越来越普遍，分子诊断率上升，与前段发育异常相关的非综合征性青光眼的不同遗传病因之间的表型重叠程度越来越明显。以无虹膜为例，虽然 突变仍然是主要原因，但在患有儿童青光眼和无虹膜的患者中也报道了 、 、 和 的变异。基于分子的视网膜和角膜疾病治疗方法正在迅速发展，青光眼和无虹膜的基因治疗临床前研究显示出有希望的结果。使用腺相关病毒载体进行基因传递最为常见，在青光眼的Tg-小鼠模型中眼压和视网膜神经节细胞存活率有所改善，并且使用CRISPR-Cas9基因编辑成功纠正了小鼠中的种系 无义变异。本综述将探讨与前段发育异常相关的非综合征性青光眼的遗传病因的作用和相互作用，并讨论这些患者分子治疗的当前进展。
